Host vascular endothelial growth factor is trophic for Plasmodium falciparum-infected red blood cells

Area of Science:

• Molecular parasitology
• Malaria pathogenesis
• Vascular biology

Background:

• Plasmodium falciparum causes severe malaria, with infected red blood cells (iRBC) sequestering in cerebral microvessels.
• Cerebral malaria pathology is linked to iRBC sequestration.
• The role of host-derived growth factors in parasite development is not fully understood.

Purpose of the Study:

• To investigate the interaction between Plasmodium falciparum and vascular endothelial growth factor (VEGF).
• To determine if iRBCs utilize host VEGF for their growth and survival.
• To explore the potential role of VEGF in cerebral malaria pathogenesis.

Main Methods:

• Immunohistochemistry on post-mortem human brain samples.
• Confocal microscopy of cultured iRBCs.
• Parasite culture experiments with and without VEGF and serum.

Main Results:

• Positive staining for VEGF was observed on iRBCs in brain tissue.
• Cultured iRBCs accumulated host VEGF within the parasitophorous vacuole and expressed host VEGF receptors (VEGF-R1, activated VEGF-R2) on their surface.
• Addition of VEGF enhanced parasite growth and partially rescued drug-impaired growth, an effect dependent on soluble VEGF receptors.

Conclusions:

• Plasmodium falciparum iRBCs can bind host VEGF receptors on the erythrocyte membrane.
• Host VEGF is accumulated within the iRBC's parasitophorous vacuole.
• Host VEGF may provide a trophic effect, supporting parasite growth and survival.